Dendritic cells and resting B cells form clusters in vitro and in vivo: T cell independence, partial LFA-1 dependence, and regulation by cross-linking surface molecules.
Initiation of an Ab response requires interaction between dendritic cells (DC), T cells, and B cells in a T cell area. We demonstrate that rat DC and B cells form T cell-independent clusters in vitro and in vivo. In vitro clusters form within 1 h and dissociate within 24 to 48 h. Clustering is restricted to resting B cells, is energy, cytoskeleton, and protein kinase C dependent, and is inhibited by anti-LFA-1 but not anti-ICAM-1 mAbs. Spleen and lymph node B cells cluster more strongly than those from lymph or blood, suggesting up-regulation of adhesiveness during transendothelial migration. Bone marrow B cells do not form clusters. DC from spleen and lymph nodes show the most clustering, lymph-borne DC are intermediate, and DC from lamina propria, Peyer's patches, and those grown from bone marrow form the fewest clusters. Clustering is stimulated by cross-linking MHC class II (whole mAb or F(ab')2) on DC or B cells or Thy-1 on DC, but not MHC class I, CD45, or CD44. Stimulation by mAb is energy, cytoskeletal, and protein kinase C dependent, but is not inhibited by anti-LFA-1 mAbs, suggesting involvement of other, unidentified adhesion molecules. We suggest that interactions between DC and B cells will occur regularly during B cell recirculation. Cross-linking of MHC class II-peptide molecules on DC by specific T cells would increase binding avidity, causing retention of Ag-specific B cells on DC long enough for the B cells to process Ag, thereby facilitating cognate interactions between T and B cells.
Kushnir
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N
Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
Liu
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L
MacPherson
G G
GG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism / Q000502:physiology*; D001402:B-Lymphocytes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D002449:Cell Aggregation / Q000187:drug effects / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002469:Cell Separation; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007399:Interphase / Q000276:immunology; D007518:Isoantibodies / Q000378:metabolism; D008196:Lymph / Q000166:cytology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*; D013897:Thoracic Duct / Q000166:cytology; D018800:Thy-1 Antigens / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; D016169:Lymphocyte Function-Associated Antigen-1; D018800:Thy-1 Antigens; C035678:anti-Thy antibody; D011493:Protein Kinase C